TREATMENT OF HUMAN LUNG-CARCINOMA XENOGRAFTS WITH A COMBINATION OF I-131-LABELED MONOCLONAL-ANTIBODY PO66 AND DOXORUBICIN

Po66, a mouse monoclonal antibody, is directed against an intracytopla smic antigen present in human lung squamous cell carcinoma cells. In p revious work it was found that the co-administration of I-125-radiolab elled Po66 and doxorubicin strongly enhanced the uptake of radioactivi ty by the tumour. The present-work was designed to evaluate, in a tumo ur-bearing mouse model of lung carcinoma, the ability of I-131-labelle d Po66 to retard tumour growth when injected alone, or in combination with doxorubicin (8 mg kg(-1) at 1-week intervals). A single dose of 5 50 mu Ci I-131-Po66 alone had no effect on tumour growth, whereas thre e fractionated doses of 250 mu Ci I-131-Po66 decreased it over two dou bling times from 14.5 +/- 1.5 days for untreated control mice to 24.8 +/- 2.7 days. Mice treated with doxorubicin alone had a double tumour doubling time of 22.6 +/- 4.9 days, compared to 35.2 +/- 2.9 days (1.5 5-fold increase) in mice treated with doxorubicin and a single dose of 550 mu Ci I-131-Po66. Doxorubicin combined with three fractionated do ses of 250 mu Ci I-131-Po66 provoked a twofold decrease in tumour grow th compared to mice treated with doxorubicin alone. The administration of fractionated doses of I-131-Po66 simultaneously with doxorubicin r esulted in a highly delayed mortality, which was not observed when I-1 31-Po66 was administered after doxorubicin. Thus, in a non-small-cell lung tumour model, a I-131-radiolabelled monoclonal antibody, directed against an intracellular antigen, significantly potentiated the effec t of chemotherapy. Such a therapeutic approach could be used as an adj uvant therapy and improve the effect of chemotherapy on distant small metastases.